Does the Affinity of Cisplatin to B-Vitamins Impair the Therapeutic Effect in the Case of Patients with Lung Cancer-consuming Carrot or Beet Juice?

2019 ◽  
Vol 19 (14) ◽  
pp. 1775-1783 ◽  
Author(s):  
Beata Szefler ◽  
Przemysław Czeleń ◽  
Adam Szczepanik ◽  
Piotr Cysewski
Keyword(s):  
Computational Study ◽  
Lone Pair ◽  
B Vitamins ◽  
Basis Set ◽  
Free Energies ◽  
Aromatic Rings ◽  
Reaction Field ◽  
Vitamin B Group ◽  
Solvation Free Energies ◽  
Derivatives Of

Background: Cisplatin (CisPt) has a well-recognized anticancer activity by interacting with DNA and inducing programmed cell death. However, theoretical studies performed on the molecular level suggest that such nonspecific interactions can also take place with many competitive compounds, such as vitamins containing aromatic rings with lone-pair orbitals. Objective: This work is a theoretical study on the initial Pt-N7(N1) bond formation with vitamins from B group and their comparison with values characterizing native purines. Methods: Geometries of studied structures were optimized with an aid of Gaussian 09 using the B3LYP functional with the 6-31G** basis set. Atomic orbitals of platinum were represented by the lanl2dz basis. Solvation free energies were evaluated by a self-consistent reaction field (SCRF) approach. A dielectric constant of 78 for water was used in the PCM continuum model computations along with radii Bondii. Results: The affinities of mono-aqua cis~[Pt(NH3)2Cl(H2O)]+ and di-aqua cis~ [Pt(NH3)2(H2O)2]2+ derivatives of Cisplatinum toward compounds belonging to the group of eight B vitamins were studied and compared to interactions with canonical purines. All the values of ΔGr unambiguously indicate that reactions with cisPt-diaqua are more preferable, but the comparison of ΔGr values obtained for compounds from vitamin B group and the ones characterizing complexes created by Guanine molecules indicates higher affinity of cisPt monomers toward purines. Conclusion: Based on the observations, the regular intake of vitamin-rich beetroot or carrot juices is strongly discouraged during anticancer therapy using CisPt drug. To confirm the results of the performed computational study, detailed clinical trials should be performed.

2-Deoxyribose Radicals in the Gas Phase and Aqueous Solution. Transient Intermediates of Hydrogen Atom Abstraction from 2-Deoxyribofuranose

2005 ◽  
Vol 70 (11) ◽  
pp. 1769-1786 ◽  
Author(s):  
Luc A. Vannier ◽  
Chunxiang Yao ◽  
František Tureček
Keyword(s):  
Aqueous Solution ◽  
Hydrogen Atom ◽  
Gas Phase ◽  
Computational Study ◽  
Hydrogen Atom Abstraction ◽  
Oh Radical ◽  
Free Energies ◽  
Intramolecular Hydrogen ◽  
Solvation Free Energies ◽  
Transient Intermediates

A computational study at correlated levels of theory is reported to address the structures and energetics of transient radicals produced by hydrogen atom abstraction from C-1, C-2, C-3, C-4, C-5, O-1, O-3, and O-5 positions in 2-deoxyribofuranose in the gas phase and in aqueous solution. In general, the carbon-centered radicals are found to be thermodynamically and kinetically more stable than the oxygen-centered ones. The most stable gas-phase radical, 2-deoxyribofuranos-5-yl (5), is produced by H-atom abstraction from C-5 and stabilized by an intramolecular hydrogen bond between the O-5 hydroxy group and O-1. The order of radical stabilities is altered in aqueous solution due to different solvation free energies. These prefer conformers that lack intramolecular hydrogen bonds and expose O-H bonds to the solvent. Carbon-centered deoxyribose radicals can undergo competitive dissociations by loss of H atoms, OH radical, or by ring cleavages that all require threshold dissociation or transition state energies >100 kJ mol-1. This points to largely non-specific dissociations of 2-deoxyribose radicals when produced by exothermic hydrogen atom abstraction from the saccharide molecule. Oxygen-centered 2-deoxyribose radicals show only marginal thermodynamic and kinetic stability and are expected to readily fragment upon formation.

scholarly journals The Affinity of Carboplatin to B-Vitamins and Nucleobases

2021 ◽  
Vol 22 (7) ◽  
pp. 3634
Author(s):  
Beata Szefler ◽  
Przemysław Czeleń ◽  
Przemysław Krawczyk
Keyword(s):  
Vitamin B6 ◽  
Pyridoxal Phosphate ◽  
Antitumor Agents ◽  
Lone Pair ◽  
Chemical Compounds ◽  
Free Energies ◽  
Aromatic Rings ◽  
Anti Cancer ◽  
Potential Impact ◽  
Reactive Molecule

Platinum compounds have found wide application in the treatment of various types of cancer and carboplatin is one of the main platinum-based drugs used as antitumor agents. The anticancer activity of carboplatin arises from interacting with DNA and inducing programmed cell death. However, such interactions may occur with other chemical compounds, such as vitamins containing aromatic rings with lone-pair orbitals, which reduces the anti-cancer effect of carboplatin. The most important aspect of the conducted research was related to the evaluation of carboplatin affinity to vitamins from the B group and the potential impact of such interactions on the reduction of therapeutic capabilities of carboplatin in anticancer therapy. Realized computations, including estimation of Gibbs Free Energies, allowed for the identification of the most reactive molecule, namely vitamin B6 (pyridoxal phosphate). In this case, the computational estimations indicating carboplatin reactivity were confirmed by spectrophotometric measurements.

scholarly journals Protonated heterocyclic derivatives of cyclopropane and cyclopropanone: classical species, alternate sites, and ring fragmentation

2015 ◽  
Vol 93 (7) ◽  
pp. 708-714 ◽  
Author(s):  
Margarida S. Miranda ◽  
Darío J.R. Duarte ◽  
Joaquim C.G. Esteves da Silva ◽  
Joel F. Liebman
Keyword(s):  
Density Functional Theory ◽  
Gas Phase ◽  
Density Functional ◽  
Computational Study ◽  
Basis Set ◽  
Proton Affinities ◽  
Functional Theory ◽  
Heterocyclic Derivatives ◽  
Gas Phase Basicities ◽  
Derivatives Of

A computational study has been performed for protonated oxygen- or nitrogen-containing heterocyclic derivatives of cyclopropane and cyclopropanone. We have searched for the most stable conformations of the protonated species using density functional theory with the B3LYP functional and the 6-31G(2df,p) basis set. More accurate enthalpy values were obtained from G4 calculations. Proton affinities and gas-phase basicities were accordingly derived.

New Model for Calculation of Solvation Free Energies:  Correction of Self-Consistent Reaction Field Continuum Dielectric Theory for Short-Range Hydrogen-Bonding Effects

1996 ◽  
Vol 100 (28) ◽  
pp. 11775-11788 ◽  
Author(s):  
Bryan Marten ◽  
Kyungsun Kim ◽  
Christian Cortis ◽  
Richard A. Friesner ◽  
Robert B. Murphy ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Short Range ◽  
Free Energies ◽  
New Model ◽  
Reaction Field ◽  
Self Consistent ◽  
Solvation Free Energies

Hydration of the carbonyl group. Further evidence for a cooperative mechanism from experimental and theoretical studies of the hydrations of formaldehyde, acetaldehyde, acetone, and cyclohexanone

1998 ◽  
Vol 76 (1) ◽  
pp. 114-124 ◽  
Author(s):  
Saul Wolfe ◽  
Zheng Shi ◽  
Kiyull Yang ◽  
Stephen Ro ◽  
Noham Weinberg ◽  
...  
Keyword(s):  
Isotope Shift ◽  
Water Clusters ◽  
Computational Procedure ◽  
Order Rate Constant ◽  
Bulk Water ◽  
Basis Set ◽  
Free Energies ◽  
Basis Set Superposition Error ◽  
Reaction Field ◽  
Water Solvent

The experimental pseudo-first-order rate constant for the neutral hydration of acetone by H218O has been determined by taking advantage of the 18O isotope shift in the 13C NMR spectrum of 2-13C-labelled acetone. With the inclusion of this result, a previously reported computational procedure has been extended, with some refinements, to the neutral hydrations of formaldehyde, acetaldehyde, acetone, and cyclohexanone by different-sized water clusters in water solvent. Excellent agreement has been achieved between the experimental free energies of activation and the free energies of activation calculated for a cyclic mechanism in which the principal reaction channel contains four nonspectator water molecules. The computational procedure predicts that the cyclic water tetramer and the cubic water octamer are the principal constituents of bulk water, in agreement with Benson's tetramer-octamer model.Key words: isotope shift, basis set superposition error (BSSE), self-consistent reaction field (SCRF), water clusters, hydration.

Synthesis, Antioxidant Activity and Theoretical Investigation of Isoxazolines Derivatives of Monoterpenoids

2019 ◽  
Vol 16 (6) ◽  
pp. 501-510
Author(s):  
Melek Gul ◽  
Serpil Eryılmaz
Keyword(s):  
Antioxidant Activity ◽  
Biological Activity ◽  
Antioxidant Activities ◽  
Computational Study ◽  
Chemical Reactivity ◽  
Radical Scavenging ◽  
Basis Set ◽  
Electrophilicity Index ◽  
Theoretical Approaches ◽  
Derivatives Of

The 3+2 cycloaddition reactions are important to generate five-membered heterocyclic compounds as well as altering biological activity effects based on structure. In the study, we synthesized new isoxazoline derivatives of different monoterpenoids and examined the structure analysis using spectroscopical analysis methods, reveal changes in the theoretical analysis related to the biological activity. These new compounds exhibit antioxidant activities; DPPH radical scavenging, ferric reducing, metal chelating activities which are significantly higher than the related commercial monoterpenoids. Theoretical approaches on the compounds containing isoxazole moiety have been performed by the DFT/B3LYP/method, 6-31G(d,p) basis set in the ground state. The global and local chemical reactivity properties of the compounds were investigated by considering the values of electronegativity, global hardness-softness, electronic chemical potential, electrophilicity index and condensed Fukui functions, local softness and local electrophilicity index. Furthermore, total energy, FMOs energy values and the dipole moment (µ), mean polarizability (α), and first order hyperpolarizability (β) values were analysed at the theoretical level to examine the polarizability characteristics of the compounds. The antioxidant activity values of the newly synthesized compounds were compared with a finding of the computational study. The results obtained exhibited good correlation on some parameters.

scholarly journals A Combined Experimental and Computational Study of Halogen and Hydrogen Bonding in Molecular Salts of 5-Bromocytosine

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3111
Author(s):  
Massimiliano Aschi ◽  
Giorgia Toto Brocchi ◽  
Gustavo Portalone
Keyword(s):  
Proton Transfer ◽  
Crystal Packing ◽  
Computational Study ◽  
Theoretical Calculations ◽  
Bromine Atom ◽  
Lone Pair ◽  
Organic Salts ◽  
Dna And Rna ◽  
Molecular Salts ◽  
Derivatives Of

Although natural or artificial modified pyrimidine nucleobases represent important molecules with valuable properties as constituents of DNA and RNA, no systematic analyses of the structural aspects of bromo derivatives of cytosine have appeared so far in the literature. In view of the biochemical and pharmaceutical relevance of these compounds, six different crystals containing proton-transfer derivatives of 5-bromocytosine are prepared and analyzed in the solid-state by single crystal X-ray diffraction. All six compounds are organic salts, with proton transfer occurring to the Nimino atom of the pyridine ring. Experimental results are then complemented with Hirshfeld surface analysis to quantitively evaluate the contribution of different intermolecular interactions in the crystal packing. Furthermore, theoretical calculations, based on different arrangements of molecules extracted from the crystal structure determinations, are carried out to analyze the formation mechanism of halogen bonds (XBs) in these compounds and provide insights into the nature and strength of the observed interactions. The results show that the supramolecular architectures of the six molecular salts involve extensive classical intermolecular hydrogen bonds. However, in all but one proton-transfer adducts, weak to moderate XBs are revealed by C–Br…O short contacts between the bromine atom in the fifth position, which acts as XB donor (electron acceptor). Moreover, the lone pair electrons of the oxygen atom of adjacent pyrimidine nucleobases and/or counterions or water molecules, which acts as XB acceptor (electron donor).

SAMPL6 Octanol-Water Partition Coefficients from Alchemical Free Energy Calculations with MBIS Atomic Charges

2019 ◽  
Author(s):  
Maximiliano Riquelme ◽  
Esteban Vöhringer-Martinez
Keyword(s):  
Free Energy ◽  
Electron Density ◽  
Free Energy Calculations ◽  
Basis Set ◽  
Energetic Cost ◽  
Atomic Charges ◽  
Free Energies ◽  
Energy Calculations ◽  
Alchemical Free Energy ◽  
Alchemical Free Energy Calculations

In molecular modeling the description of the interactions between molecules forms the basis for a correct prediction of macroscopic observables. Here, we derive atomic charges from the implicitly polarized electron density of eleven molecules in the SAMPL6 challenge using the Hirshfeld-I and Minimal Basis Set Iterative Stockholder(MBIS) partitioning method. These atomic charges combined with other parameters in the GAFF force field and different water/octanol models were then used in alchemical free energy calculations to obtain hydration and solvation free energies, which after correction for the polarization cost, result in the blind prediction of the partition coefficient. From the tested partitioning methods and water models the S-MBIS atomic charges with the TIP3P water model presented the smallest deviation from the experiment. Conformational dependence of the free energies and the energetic cost associated with the polarization of the electron density are discussed.

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